CRYOSURGERY FOR TREATMENT O F TRICHIASIS

J O H N H. SULLIVAN, M.D., C R O W E L L BEARD, M.D., AND J O H N D. BULLOCK, M.D.

San Francisco, California

Surgical techniques to repair trichiasis1

occasionally require skills of consider­able complexity, are time consuming, and the functional and cosmetic results are often less than optimum. Mechanical epi-lation provides only temporary relief. A permanent effect can be anticipated with proper use of electrolysis when few lash­es are involved. When many aberrant lashes are present, galvanic or diathermy current is less successful and may result in cicatrization of the eyelid margin and additional cilia growth. Recurrent trichia­sis is a common problem after any meth­od of treatment.

The necrotizing effect of cryotherapy has been used in the treatment of skin disorders such as basal cell carcinoma.2,3

Treatment of such tumors of the eyelid by cryosurgery4·5 led to the observation that eyelashes included in the frozen area were permanently destroyed, and that cryosurgery could be used in the treat­ment of the vexing problem of trichiasis. To investigate therapeutic possibilities, we performed experiments on rabbits and used this information in a clinical study of selected patients with trichiasis.

M A T E R I A L AND M E T H O D S

Animal studies—To determine the ef­fect on regeneration of cilia we subjected eyelash follicles of rabbits to cryosurgical lesions at specified temperatures.

Eleven adult male and female albino

From the Department of Ophthalmology, Univer­sity of California, San Francisco. Dr. Bullock was a Heed fellow (1974-1975).

Presented at the 112th annual meeting of the American Ophthalmological Society, Kamuela, Ha­waii, May 15, 1976.

Reprint requests to John H. Sullivan, M.D., De­partment of Ophthalmology, University of Califor­nia Medical Center, San Francisco, CA 94143.

rabbits received 20 mg/kg of intravenous sodium pentobarbital for anesthesia. A segment of the eyelid margin of both upper eyelids in each rabbit was treated by cryosurgery at one of four tempera­tures: - 5 ° , -15° , -30° , and -70° C. Tis­sue temperature was monitored by a mic-rothermocouple needle implanted 2 mm from the eyelid margin. Lesions were applied with a cryosurgical instrument by using liquid nitrogen circulating through a 5-mm diameter metal probe. The probe was applied directly to the eyelid margin with minimum pressure. When the tem­perature reached its designated level, the probe was removed. The tissue was al­lowed to return to body temperature and the procedure was repeated. Antibiotic ointment was applied to the eyelids and the animals were returned to their indi­vidual cages.

After eight weeks, the animals were killed and we made sections through the eyelids in the region of treatment. Paraf­fin sections were stained with hematoxy-lin and eosin and Masson's trichrome stain. Representative sections were matched with controls and compared for microscopic alteration in eyelid structure.

Clinical studies—We selected 23 pa­tients for cilia cryoablation and observed them for six to 14 months. We used sever­al instruments and methods to produce the cryosurgical lesion. In all instances a cutaneous application of a coolant was made at the eyelid margin. We used lido-caine 1% (Xylocaine) with epinephrine 1:100,000 routinely as an infiltration an­esthetic since epinephrine had facilitated rapid freezing and slow thawing by vaso­constriction.6 Our initial experience with nitrous oxide using the Amoils retinal probe was discouraging. Liquid nitrogen

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118 AMERICAN JOURNAL OF OPHTHALMOLOGY JULY, 1976

was used either in a contained system, circulating through a metal probe, or as a direct spray. Direct liquid spray and va­porized spray were equally effective. Ad­jacent skin surfaces were protected by circumscribing the affected region with paper tape. Tape was also used to secure a nonmetallic eyelid plate in the conjuncti-val fornix to protect the cornea (Fig. 1). We used a microthermocouple implanted in the epitarsal region, 2 to 3 mm from the eyelid margin, to monitor the temperature. Within seconds, the treated region be­came white and hard. A temperature of -30°C usually was attained in 30 to 45 seconds. Spontaneous thawing proceed­ed, sometimes taking five minutes. Dur­ing refreezing the desired temperature was usually reached within ten to 15 seconds.

R E S U L T S

Animal studies—Eyelids treated at -5°C retained a full complement of eye­lashes and could not be distinguished from the eyelids of control animals; no histologie alterations were present (Fig. 2).

At-15°C, few clinical changes were

Fig. 1 (Sullivan, Beard, and Bullock). Patient is prepared for surgery.

Fig. 2 (Sullivan, Beard, and Bullock). Top, Rabbit eyelid at -5°C. Bottom, Rabbit eyelid at -5°C (xlO).

apparent (Fig. 3, top). Some specimens showed loss of cilia along the eyelid mar­gin. Histopathology consisted of cutane­ous and conjunctival epithelial hypertro­phy. Minimal tissue disorganization was present. Occasionally, hair follicles showed vacuolization and disorganiza­tion in the bulb (Fig. 3, bottom).

Eyelids treated at -30°C retained their general appearance but alopecia was pre­sent in the treated region (Fig. 4, top). Microscopic examination showed scar tis­sue formation in the deeper eyelid struc­tures. Epithelial surfaces were hyperplas-tic and sebaceous glands were reduced in size (Fig. 4, bottom). The amount of reac­tion varied from one specimen to another. Regenerating cilia were present in one instance.

Severe reaction resulted from treatment at -70°C (Fig. 5, top). Secondary infec­tion was often present. Total loss of lash­es occurred in all eyelids. In many speci­mens, eyelid structures appeared to be totally replaced by scar tissue. Sebaceous

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Fig. 3 (Sullivan, Beard, and Bullock). Top, Rabbit eyelid at -15°C. Bottom, Rabbit eyelid at -15°C (xlO). glands were frequently the only recogniz­able structure (Fig. 5, bottom).

A precise dose-response relationship Fig. 5 (Sullivan, Beard, and Bullock). Top, Rabbit eyelid at -70°C. Bottom, Rabbit eyelid at -70°C (xlO).

Fig. 4 (Sullivan, Beard, and Bullock). Top, Rabbit eyelid at -30°C. Bottom, Rabbit eyelid at -30°C (xlO).

between the loss of cilia and the magni­tude of cryosurgery cannot be made be­cause of the technical difficulty in moni­toring and controlling a reproducible cryogenic reaction (Fig. 6). However, temperatures cooler than — 15°C were re­quired for cilia cryoablation and tempera­tures below -70°C were undesirable and unnecessary. A temperature of — 30°C ap­pears to be within the range at which irreversible follicular damage occurs, using the double, rapid-freeze, slow-thaw technique. Most specimens treated at -30°C achieved alopecia without other clinically observable alterations of eyelid structure or function.

Clinical studies—In successfully treat­ed cases, we noted moderate edema, occa­sionally with bullae formation, in the first 12 hours. When extensively treated, the eyelids were swollen closed in the first 48 hours. There was little associated pain.

120 AMERICAN JOURNAL OF OPHTHALMOLOGY JULY, 1976

5

4 < u 3 a.

1 -

:r LOSS OF ALL LASHES Fig. 6 (Sullivan, Beard, and Bullock). Alopecia as a function of attained temperature.

i I i +37°C -5°-15° -30°

I ' -70° -100°C

TEMPERATURE With severe reactions, antibiotic ointment was prescribed.

The maximum reaction generally oc­curred between 48 and 72 hours. If the treated cilia were grasped with forceps then, there was little resistance to epilat-ion. Seven to ten days after surgery, the reaction had generally subsided and most cilia shed spontaneously. Lashes broken

Fig. 7 (Sullivan, Beard, and Bullock). Top, Trichi-asis in patient's right lower eyelid. Bottom, Right lower eyelid, four months after cryosurgery.

at the skin surface sometimes persisted in the root sheath for several months, al­though there was no resistance to their epilation. The reaction in most instances consisted of moderate tissue swelling and exudation on the cutaneous surface. A thin eschar often formed, but prompt sur­face epithelialization was the rule. The conjunctival surface resisted damage and was quick to recover. There was no clini­cally obvious loss of tissue, and cicatricial distortion of the eyelid was not observed (Fig. 7). In successfully treated areas, meibomian gland secretions were not vis­ible by slit-lamp biomicroscopy. Loss of cutaneous pigmentation frequently oc­curred. Histopathologic correlation of these clinical findings was not available.

We observed recurrent trichiasis in five instances after the use of liquid nitrogen. In these cases, the end point for the duration of application of cryosurgery was the appearance of the iceball. Ther­mocouple monitoring was not performed. In two of these cases, a single freeze-thaw cycle was used. Regrowth of lashes oc­curred within four weeks. Retreatment by double freeze-thaw cycle with the use of a tissue temperature monitor was success­ful in all cases.

DISCUSSION

Cryonecrosis is a complex biophysical

VOL. 82, NO. 1 TRICHIASIS 121

reaction caused by changes in tissue sol­ute concentration, ice formation, and vas­cular stasis.2*7,8 The necrotizing îeaction is enhanced by repeated cycles of rapid freezing and slow thawing.9 Various tis­sues have different susceptibilities to irre­versible damage from freezing.10,11 The hair follicle is relatively sensitive to the effects of freezing.12-15

The results of this study indicate the importance of achieving an adequate tissue temperature that destroys the lash follicle. Direct spray of liquid or vapo­rized liquid nitrogen was the most effec­tive method of cutaneous application of coolant. Prolonged exposure to the cool­ant resulted in a larger area of damage, and tissue temperature cooler than —30CC was associated with increased necrosis and scar formation within the center of the iceball. To assure delivery of the minimum effective dosage, tissue temper­ature monitoring is obligatory.

With this technique it is difficult to destroy selectively only two or three lash­es. The minimum area of alopecia pro­duced is approximately 3 mm in diameter. Alternate methods of repair may be more suitable in patients with a small segment of trichiasis in the upper eyelid who are concerned about the cosmetic result.

Addendum—Since this paper was pre­pared, we have had additional experience using oculoplastic nitrous oxide cooled probes (Cryomedics). Tissue tempera­tures of at least -20°C were obtained at the level of the lash follicles. This was sufficient for lash ablation. The surface reactions are less than those resulting from nitrogen spray. We suggest the stan­dard retinal probe, although cooled by nitrous oxide, should not be relied upon unless tissue temperature is monitored.

SUMMARY

We cryosurgically destroyed eyelashes in rabbits and applied the technique to treat 23 selected patients with trichiasis.

Liquid nitrogen was sprayed on the eye­lid margin by using a double, rapid-freeze, slow-thaw cycle monitored by a subcutaneous thermocouple to -30°C. It was an improvement on electrolysis and a simple alternative to surgery.

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